The proposed ICIDR program comprises a multidisciplinary and coordinated set of epidemiological, clinical, and laboratory research activities in enteric parasitic disease, and will specifically focus on giardiasis and cryptosporidiosis. A major integrating theme will be to determine relationships between manifestation of infection in the host, and characteristics of the host and of the parasite. We will explore how the clinical expression of infection relates to the environmental, nutritional, and immunological status of the infected child and to genetic and/or antigenic variability of the parasite. The proposed ICIDR will be organized as 4 Research Projects and 4 Core Components and will be a collaborative program among investigators from U.S. institutions (Columbia University, Cornell University) and institutions in Israel and adjacent areas (Hebrew University, Ben Gurion University, Ramallah Hospital). Project A will prospectively follow the natural history of G. lamblia and Cryptosporidium infections in a cohort of newborn children for three years in a Bedouin village in the Negev, and will determine the interactions of growth and nutrition of these children with symptomatic and asymptomatic infections with these parasites. Because the cohort study will not provide a sufficient number of cases to explore in depth associations between symptomatic infec- tions with nutrition and malnutrition chronic diarrhea and immunologic status. Project B will do so in case control studies of diarrhea associated with these two Parasites in different population settings; hosPitalized children in Jerusalem and in the West bank and ambulatory children ar a West bank primary health center and in 3 kibbutzim. Project C will Probe the distribution of strain diversity of G. lamblia and Cryptosporidium using the immunologic response isoenzyme comParisons antigenic analysis, and DNA sequence analysis (Pulsed field gel-electroPhoresis) on isolates to be obtained in Projects A and B. Project D aims to investigate the mechanism regulating strain variability in G. lamblia and to determine whether antigenic diversity results from changes in the DNA sequence itself, or from variable gene expression (or both). The 4 Core components include: A) ICIDR administration at Columbia University; B) a coordination Core in Israel; C) an immunology Core laboratory and; D) a Core biostatistics resource. The program will, therefore, integrate basic molecular genetic and immunologic analysis with what is expressed in different population and clinical settings.